Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform

DOI record: { "DOI": "10.1101/2023.01.20.23284849", "URL": "http://dx.doi.org/10.1101/2023.01.20.23284849", "abstract": "<jats:p>Objective: To compare the effectiveness of Paxlovid vs. sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients. Design: With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Setting: Patient-level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death within the OpenSAFELY-TPP platform, covering a period where both Paxlovid and sotrovimab were first-line treatment options in community settings. Participants: Non-hospitalised adult COVID-19 patients at high risk of severe outcomes treated with Paxlovid, sotrovimab or molnupiravir between February 11, 2022 and October 1, 2022. Interventions: Paxlovid, sotrovimab or molnupiravir administered in the community by COVID-19 Medicine Delivery Units. Main outcome measure: COVID-19 related hospitalisation or COVID-19 related death within 28 days after treatment initiation. Results: A total of 7683 eligible patients treated with Paxlovid (n=4836) and sotrovimab (n=2847) were included in the main analysis. The mean age was 54.3 (SD=14.9) years; 64% were female, 93% White and 93% had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 52 (0.68%) COVID-19 related hospitalisations/deaths were observed (33 (0.68%) treated with Paxlovid and 19 (0.67%) with sotrovimab). Cox proportional hazards model stratified by region showed that after adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, treatment with Paxlovid was associated with a similar risk of outcome event as treatment with sotrovimab (HR=1.14, 95% CI: 0.62 to 2.08; P=0.673). Results from propensity score weighted Cox model also showed comparable risks in these two treatment groups (HR=0.88, 95% CI: 0.45 to 1.71; P=0.700). An exploratory analysis comparing Paxlovid users with 802 molnupiravir users (11 (1.37%) COVID-19 related hospitalisations/deaths) showed some evidence in favour of Paxlovid but with variation in the effect estimates between models (HR ranging from 0.26 to 0.61). Conclusion: In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received Paxlovid and sotrovimab between February and October 2022, when different subvariants of Omicron were dominant.</jats:p>", "accepted": { "date-parts": [ [ 2023, 1, 22 ] ] }, "author": [ { "affiliation": [], "family": "Zheng", "given": "Bang", "sequence": "first" }, { "affiliation": [], "family": "Tazare", "given": "John", "sequence": "additional" }, { "affiliation": [], "family": "Nab", "given": "Linda", "sequence": "additional" }, { "affiliation": [], "family": "Mehrkar", "given": "Amir", "sequence": "additional" }, { "affiliation": [], "family": "MacKenna", "given": "Brian", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-5127-4728", "affiliation": [], "authenticated-orcid": false, "family": "Goldacre", "given": "Ben", "sequence": "additional" }, { "affiliation": [], "family": "Douglas", "given": "Ian J", "sequence": "additional" }, { "affiliation": [], "family": "Tomlinson", "given": "Laurie", "sequence": "additional" }, { "affiliation": [], "name": "The OpenSAFELY Collaborative", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 1, 23 ] ], "date-time": "2023-01-23T06:05:17Z", "timestamp": 1674453917000 }, "deposited": { "date-parts": [ [ 2023, 1, 23 ] ], "date-time": "2023-01-23T06:05:18Z", "timestamp": 1674453918000 }, "group-title": "Epidemiology", "indexed": { "date-parts": [ [ 2023, 1, 24 ] ], "date-time": "2023-01-24T05:56:44Z", "timestamp": 1674539804597 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2023, 1, 22 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2023.01.20.23284849", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2023, 1, 22 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2023, 1, 22 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "http://medrxiv.org/lookup/doi/10.1101/2023.01.20.23284849" } }, "score": 1, "short-title": [], "source": "Crossref", "subtitle": [], "subtype": "preprint", "title": "Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform", "type": "posted-content" }